Background and objective: The risk of myelin oligodendrocyte glycoprotein antibody–associated disease relapses in new-onset patients and whether this is modified by immunotherapies is uncertain. Method: To assess relapse risk, we conducted a retrospective population-based cohort study of people with myelin oligodendrocyte glycoprotein antibody–associated disease diagnosed at symptom onset during 2019–2024. Results: We identified 69 eligible patients (mean age = 27.6 years), 30 (43.5%) were under 18 years old, and 36 (52.2%) were female. Corticosteroids were initiated within 8 days (median, interquartile range = 5–17) after symptom onset in most patients (n = 65). Twenty-two patients (31.9%) were treated acutely with other immunotherapies, but only 11 (15.9%) received empiric prophylaxis. After a median follow-up of 31.9 months (interquartile range = 23.0–48.9), most (n = 57, 82.6%) had made full recoveries; only three (10.0%) pediatric and five of 39 (12.8%) adult patients relapsed; and only three (4.3%) were left with moderate-to-severe deficits (all relapse-free). There was no significant association between demographic, clinical or treatment characteristics and relapse risk. Conclusion: These findings are reassuring for people with myelin oligodendrocyte glycoprotein antibody–associated disease diagnosed at symptom onset. The risk of relapse and permanent deficits appears to be low even without prophylactic immunotherapy or prolonged corticosteroid tapers when onset symptoms are treated promptly with corticosteroids and/or other immunotherapies.
Sensory symptoms are common in multiple sclerosis, but atypical manifestations remain under-recognized, contributing to diagnostic delay. We report a 34-year-old woman with bilateral limb paresthesias and a positive Lhermitte’s sign who subsequently developed a new-onset episodic rectal vibratory sensation (pallesthesia). Magnetic resonance imaging demonstrated demyelinating lesions at C2/3, T9, an equivocal conus medullaris lesion, and disseminated brain involvement. Alternative inflammatory diagnoses were excluded. To our knowledge, this is the first documented case of rectal pallesthesia as a manifestation of multiple sclerosis, underscoring the need to consider central demyelinating pathologies in unexplained pelvic sensory disturbances.
Adaptive immune mechanisms, including CD8 T cell–mediated neuroinflammation, are increasingly implicated in Alzheimer’s disease. We examined whether exposure to natalizumab, an α4-integrin antagonist that restricts leukocyte trafficking into the central nervous system, was associated with Alzheimer’s disease prevalence among older adults with multiple sclerosis. Using Epic Cosmos electronic health record data, we identified 875,226 individuals with MS, of whom 9095 had an Alzheimer’s disease diagnosis after age 65 years. Alzheimer’s disease prevalence differed significantly across disease-modifying therapies, with natalizumab-treated patients demonstrating the lowest prevalence (0.13%; 95% confidence interval: 0.10–0.17%). These findings demonstrate a lower recorded prevalence of late-life Alzheimer’s disease among natalizumab-exposed patients; however, given the aggregated nature of the data, this observation should be considered descriptive and hypothesis-generating.
Background: In relapsing multiple sclerosis trials, reductions in annualized relapse rate and gadolinium-enhancing lesions often diverge, potentially due to misclassification of pseudoexacerbations as relapses. We evaluated whether incorporating magnetic resonance imaging evidence into relapse definitions improves specificity and apparent treatment effect. Objectives: We performed post hoc analyses of the ULTIMATE I and II phase 3 trials comparing ublituximab versus teriflunomide. Relapses were adjudicated per protocol (Expanded Disability Status Scale/Functional System Scales criteria). We applied increasingly stringent clinical criteria and a magnetic resonance imaging–supported relapse definition (new T2 lesion). Annualized relapse rate was modeled using a generalized estimating equation with exposure offset. Power/sample size implications were estimated. Results: Protocol-defined annualized relapse rate reduction with ublituximab was 54.2% (annualized relapse rate: 0.084 vs 0.183). Stringent clinical criteria modestly increased reduction to 60.1%. Magnetic resonance imaging–supported relapses markedly amplified the effect to 87.5% (rate ratio: 0.125), with Year 2 reduction to 92.8%. Most ublituximab relapses (77.3%) lacked magnetic resonance imaging activity versus teriflunomide (17.8%). Power analyses indicated approximately a two-thirds sample size reduction using magnetic resonance imaging–supported relapses. Conclusion: Requiring magnetic resonance imaging evidence substantially increases specificity of relapse ascertainment, unmasks treatment effects of high-efficacy therapy, and improves trial efficiency. Prospective validation of magnetic resonance imaging–supported relapse definitions as complementary/alternative endpoints in relapsing multiple sclerosis trials is warranted, plus further corroboration with other biomarkers of disease activity toward a truly biologically verified relapse definition.
